Protective effect of luteolin on skin ischemia-reperfusion injury through an AKT-dependent mechanism.

Cutaneous ischemia­reperfusion (I/R) injury is one of the most crucial problems in flap surgery, which affects the survival of the skin flap and patient prognosis, luteolin, a plant derived flavonoid, has previously been shown to exert a variety of beneficial effects for reducing I/R injury in several organs. The aim of the present study was to evaluate the anti­inflammatory and anti­oxidative stress effects of luteolin on cutaneous I/R injury. The in vitro study were performed using a permanent human immortalized epidermal keratinocyte cell line (HaCaT), cells were cultured in the presence of luteolin and were then treated with hydrogen peroxide, the cell viability, mitochondrial membrane potential and the cell survival/apoptosis related signaling pathway activation were assessed to investigate the cytoprotective effects of luteolin. For in vivo experiments, skin flap I/R injury animal model was established in Sprague­Dawley rats, by measuring the area of flap survival, analyzing the expression of pro­inflammatory cytokine and evaluation of the histological changes in the skin tissue, the protective effects of luteolin on skin I/R injury were investigated. The function of protein kinase B (AKT) and heme oxygenase­1 (HO­1) activation on luteolin mediated I/R injury protection was assessed by administration of phosphoinositide­3­kinase/AKT inhibitor LY294002 and HO­1 inhibitor ZNPP. The results showed that luteolin treatment significantly increased the viability of HaCaT cells upon exposure to hydrogen peroxide, and the administration of luteolin in vivo significantly improved skin flap survival in the I/R injury rat model. The mechanisms underlying these beneficial effects included increased phosphoinositide­3­kinase/protein kinase B activation, improved expression of antioxidant enzyme, and scavenging the cytotoxic effects of reactive oxygen species (ROS). Taken together, the results suggested that luteolin preconditioning yielded significant protection against cutaneous I/R injury by protecting skin keratinocytes from ROS­induced damage.

O-6-methylguanine-DNA Methyltransferase Inhibits Gastric Carcinoma Cell Migration and Invasion by Downregulation of Matrix Metalloproteinase 2.

MGMT plays a key role in many kinds of cancers. However, the molecular mechanisms of MGMT involvement in gastric cancer (GC) are poorly elucidated. Here, we investigated the role of MGMT in GC cell migration, invasion and metastatic potential. Our data showed that MGMT expression was negatively correlated with lymph node metastasis and late TNM stages. These findings were accompanied by downregulation of matrix metalloproteinase 2 (MMP2). Loss of MGMT expression induced increases in GC cell metastasis and invasion potential in vitro and in vivo. These effects were reversed by inhibition of MGMT and MMP2. MGMT overexpression downregulated MMP2 protein levels, whereas this effect was counteracted by MGMT siRNA. In summary, MGMT is involved in gastric carcinogenesis via downregulation of MMP2. The MGMT/MMP2 pathway plays an essential role in GC metastasis and may be a potential therapeutic target for GC treatment.

Up-regulated Circulating miR-106a by DNA Methylation Promised a Potential Diagnostic and Prognostic Marker for Gastric Cancer.

Previous studies suggested that abnormal miRNA expression was a significant characteristic of malignant tumors. We aimed to explore the role of miR-106a as the potential diagnostic and prognostic biomarker in gastric cancer (GC). Firstly, the expression level of miR-106a was detected by qPCR in 28 pairs of GC cancer tissues and adjacent tissues, 48 pairs of plasma samples before and after operation from GC patients, and 22 plasma samples from healthy controls. It had revealed that the level of miR-106a in tumor tissues (2.700±2.565) was significantly higher compared to adjacent tissues (1.321±0.904) (p<0.05). Besides, the expression level of miR-106a in plasma of GC (9.479±5.595) was significantly up-regulated compared with healthy controls (2.594±2.329) (p<0.05), while a remarkable decline of miR- 106a expression was observed in plasma of GC patients after gastrectomy. Further statistic data showed high miR-106a expression was closely related to the degree of lymphatic metastasis and TNM staging of GC. We also applied ROC curve in order to evaluate miR-106a as a diagnostic marker for GC patients. As a result, the sensitivity and specificity were 60.4%, 68.2% in tissue samples and 72.9%, 63.6% in plasma samples, respectively. At last, we explored the methylation status of miR-106a promoter in 28 paired GC tissues through methylation-specific PCR (MSP), the result showed that the methylation rate was 53.6% in cancer tissues and 85.7% in adjacent tissues. Moreover, the result indicated that promoter hypomethylation of miR- 106a is related to its high expression. Our research indicated that miR-106a might serve as a potential prognostic indicator in progressive GC and up-regulated circulating miR-106a by promoter hypomethylation, might be proposed as a candidate diagnostic and prognostic indicator for GC.

[Clinical observation of breast hyperplasia treated with auricular point sticking therapy and Xiaopijian].

OBJECTIVE: To observe the efficacy difference in the treatment of breast hyperplasia between the combined therapy of auricular point sticking and Xiaopijian and the simple application of Xiaopijian. METHODS: Ninety-one patients were randomized into an observation group (46 cases) and a control group (45 cases). In the observation group, the sticking therapy on the auricular points was applied in combination with the oral medication of Chinese herbal medicine, Xiaopijian. Auricular points included Ruxian, Neifenmi (CO18), Luanchan, Shenmen (TF4), Gan (CO2), Pi (CO13). The auricular point sticking therapy was applied once a week on the auricular points of one side alternatively. Xiaopijian was the self-prepared decoction. The main ingredients are radix bupleuri Bupleurum chinense, spica prunellae prunella vulgaris and radix peoniae alba Paeonia lactiflora, 30 mL each time, three times a day. In the control group, Xiaopijian was simply prescribed for oral administration, 30 mL each time, 3 times a day. The treatment was discontinued during menstruation in the two groups. The menstrual cycle of one month made one session of treatment. The treatments for 3 sessions were observed. The scores of symptoms and physical signs, including the degree of breast pain, hardness and size of breast masses as well as the scores of general and supplementary symptoms were compared before and after treatment in the patients of the two groups. The clinical efficacy was compared between the two groups. RESULTS: After treatment, the scores of symptoms and physical signs were reduced apparently as compared with those before treatment in the patients of the two groups (both P<0. 05). The score reduction in the observation group was much more than that in the control group (11.02±1. 78 vs 9.82±1. 53, P<0. 05). The total effective rate was 95.7% (44/46) in the observation group, higher apparently than 80. 0% (36/45, P<0. 05). CONCLUSION: The combined therapy of auricular point sticking and Xiaopijian achieves the superior efficacy on breast hyperplasia as compared with the simple application of Xiaopijian.

Clinical and prognostic relevance of EZH2 in breast cancer: A meta-analysis.

The polycomb group protein enhancer of zeste homolog 2 (EZH2) is regarded as a tightly linking oncogene in many types of cancer. However, the prognostic role of EZH2 in breast cancer (BC) still remains controversial. Our study aimed to evaluate the clinical and prognostic relevance of EZH2 in BC patients based on published studies. 11 studies totally containing 2330 patients (1052 EZH2-positive and 1278 EZH2-negative) were included in our meta-analysis. Our data showed that EZH2 over-expression was significantly associated with estrogen receptor (ER) negativity [OR=0.227, 95% CI=0.174-0.297, P=0.000], progesterone receptor (PR) negativity [OR=0.454, 95% CI=0.300-0.687, P=0.000], human epidermal growth factor receptor type 2 (HER-2) positivity [OR=1.846, 95% CI=1.366-2.496, P=0.000], invasive ductal cancer (IDC) [OR=2.237, 95% CI=1.489-3.361, P=0.000], race (Caucasian) [OR=0.707, 95% CI=0.522-0.957, P=0.025], high histological grade [OR=3.177, 95% CI=2.012-5.014, P=0.000] and triple-negative status (TNBCs) [OR=5.380, 95% CI=1.065-27.187, P=0.042], which led to a poor OS rate in BC [RR=2.193, 95% CI=1.495-3.217, P=0.000]. In conclusion, EZH2 participated in the progression of BC as a putative factor, and over-expression of EZH2 was distinctly correlated with a poor patient survival. EZH2 may serve as a prognostic biomarker and target in BC patients.

Simultaneous idiopathic segmental infarction of the great omentum with spontaneous splenic rupture: a rare association.

Idiopathic segmental infraction of the greater omentum (ISIGO) is a rare cause of acute abdomen. One of the main symptoms is right-side abdominal pain, while its etiology is still unclear. Until now, ISIGO simultaneously with spontaneous splenic rupture (SSR) has not been reported. Here, we presented a case of a 35-year old man, who was admitted with an acute abdomen, and the clinical diagnosis was ISIGO with SSR. He had a significant previous medical history of the vein thrombosis of lower limbs. Partial omental resection and splenectomy were performed, and the postoperative recovery of the patient was excellent. We also highlighted several possible theories to explain the etiology of the ISIGO, and emphasized that surgical methods, including laparoscopic surgery and laparotomy, are still the best way to treat the ISIGO at the emergency condition.

Prognostic significance of Beclin-1 expression in colorectal cancer: a meta-analysis.

OBJECTIVE: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers. However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed to evaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients. MATERIALS AND METHODS: All related studies were systematically searched in Pubmed, Embase, Springer and Chinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed to determine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were included in our analysis. RESULTS: Our data showed that high Beclin-1 expression in patients with CRC was associated with poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overall survival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1 over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was no evidence of publication bias as suggested by Egger's tests for tumor distant metastasis (p=1.000), differentiation (p=1.000) and OS (p=0.308). CONCLUSIONS: Our present meta-analysis indicated that elevated Beclin-1 expression iss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as an efficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.